Variant 3-122913008-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_001031702.4(SEMA5B):c.2560G>T(p.Gly854Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000699 in 1,603,144 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000061 ( 2 hom. )

Consequence

SEMA5B
NM_001031702.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SEMA5B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.792

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5B	NM_001031702.4 linkuse as main transcript	c.2560G>T	p.Gly854Trp	missense_variant	18/23	ENST00000357599.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5B	ENST00000357599.8 linkuse as main transcript	c.2560G>T	p.Gly854Trp	missense_variant	18/23	1	NM_001031702.4		Q9P283-1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000414

AC:

AN:

217238

Hom.:

AF XY:

0.0000250

AC XY:

AN XY:

119898

show subpopulations

Gnomad AFR exome

AF:

0.0000796

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000186

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000323

Gnomad OTH exome

AF:

0.000376

GnomAD4 exome

AF:

0.0000613

AC:

AN:

1450984

Hom.:

Cov.:

AF XY:

0.0000499

AC XY:

AN XY:

721246

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000632

Gnomad4 OTH exome

AF:

0.00112

GnomAD4 genome

AF:

0.000151

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.0000423

AC:

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.2560G>T (p.G854W) alteration is located in exon 18 (coding exon 17) of the SEMA5B gene. This alteration results from a G to T substitution at nucleotide position 2560, causing the glycine (G) at amino acid position 854 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

0.83

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.97

D;D;D;D;.;D;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.79

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.72

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

Polyphen

1.0

.;.;D;.;D;.;.

Vest4

0.75, 0.76, 0.72, 0.73

MutPred

0.78

.;.;Loss of disorder (P = 0.0172);.;Loss of disorder (P = 0.0172);.;Loss of disorder (P = 0.0172);

MVP

0.83

MPC

1.0

ClinPred

0.91

GERP RS

5.0

Varity_R

0.90

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over